105 research outputs found

    Algorithms and literate programs for weighted low-rank approximation with missing data

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    Linear models identification from data with missing values is posed as a weighted low-rank approximation problem with weights related to the missing values equal to zero. Alternating projections and variable projections methods for solving the resulting problem are outlined and implemented in a literate programming style, using Matlab/Octave's scripting language. The methods are evaluated on synthetic data and real data from the MovieLens data sets

    Mouse precision-cut liver slices as an ex vivo model to study drug-induced cholestasis

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    Drugs are often withdrawn from the market due to the manifestation of drug-induced liver injury (DILI) in patients. Drug-induced cholestasis (DIC), defined as obstruction of hepatic bile flow due to medication, is one form of DILI. Because DILI is idiosyncratic, and the resulting cholestasis complex, there is no suitable in vitro model for early DIC detection during drug development. Our goal was to develop a mouse precision-cut liver slice (mPCLS) model to study DIC and to assess cholestasis development using conventional molecular biology and analytical chemistry methods. Cholestasis was induced in mPCLS through a 48-h-incubation with three drugs known to induce cholestasis in humans, namely chlorpromazine (15, 20, and 30 µM), cyclosporin A (1, 3, and 6 µM) or glibenclamide (25, 50, and 65 µM). A bile-acid mixture (16 µM) that is physiologically representative of the human bile-acid pool was added to the incubation medium with drug, and results were compared to incubations with no added bile acids. Treatment of PCLS with cholestatic drugs increased the intracellular bile-acid concentration of deoxycholic acid and modulated bile-transporter genes. Chlorpromazine led to the most pronounced cholestasis in 48 h, observed as increased toxicity; decreased protein and gene expression of the bile salt export pump; increased gene expression of multidrug resistance-associated protein 4; and accumulation of intracellular bile acids. Moreover, chlorpromazine-induced cholestasis exhibited some transition into fibrosis, evidenced by increased gene expression of collagen 1A1 and heatshock protein 47. In conclusion, we demonstrate that mPCLS can be used to study human DIC onset and progression in a 48 h period. We thus propose this model is suited for other similar studies of human DIC

    A stepwise transformation:description and outcome of perioperative procedures in patients receiving a total knee arthroplasty

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    Aims To investigate the impact of consecutive perioperative care transitions on in-hospital recovery of patients who had primary total knee arthroplasty (TKA) over an 11-year period. Methods This observational cohort study used electronic health record data from all patients undergoing preoperative screening for primary TKA at a northern netherlands hospital between 2009 and 2020. In this timeframe, three perioperative care transitions were divided into four periods: Baseline care (Joint Care, n = 171; May 2009 to August 2010), Function-tailored (n = 404; September 2010 to October 2013), Fast-track (n = 721; november 2013 to May 2018), and Prehabilitation (n = 601; June 2018 to December 2020). In-hospital recovery was measured using inpatient recovery of activities (IROA), length of stay (LOS), and discharge to preoperative living situation (PLS). Multivariable regression models were used to analyze the impact of each perioperative care transition on in-hospital recovery. Results The four periods analyzed involved 1,853 patients (65.9% female (1,221/1,853); mean age 70.1 years (SD 9.0)). IROA improved significantly with each transition: Function-tailored (0.9 days; p &lt; 0.001 (95% confidence interval (CI) -0.32 to -0.15)), Fast-track (0.6 days; p &lt; 0.001 (95% CI -0.25 to -0.16)), and Prehabilitation (0.4 days; p &lt; 0.001 (95% CI -0.18 to -0.10)). LOS decreased significantly in Function-tailored (1.1 days; p = 0.001 (95% CI -0.30 to -0.06)), Fast-track (0.6 days; p &lt; 0.001 (95% CI -0.21 to -0.05)), and Prehabilitation (0.6 days; p &lt; 0.001 (95%CI -0.27 to -0.11)). Discharge to PLS increased in Function-tailored (77%), Fast-track (91.6%), and Prehabilitation (92.6%). Post-hoc analysis indicated a significant increase after the transition to the Fast-track period (p &lt; 0.001 (95% CI 3.19 to 8.00)). Conclusion This study highlights the positive impact of different perioperative care procedures on in-hospital recovery of patients undergoing primary TKA. Assessing functional recovery, LOS, and discharge towards PLS consistently, provides hospitals with valuable insights into postoperative recovery. This can potentially aid planning and identifying areas for targeted improvements to optimize patient outcomes.</p

    Accumulation of fibronectin in the heart after myocardial infarction: a putative stimulator of adhesion and proliferation of adipose-derived stem cells

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    Stem cell therapy is a promising treatment after myocardial infarction (MI). A major problem in stem cell therapy, however, is that only a small proportion of stem cells applied to the heart can survive and differentiate into cardiomyocytes. We hypothesized that fibronectin in the heart after MI might positively affect stem cell adhesion and proliferation at the site of injury. Therefore, we investigated the kinetics of attachment and proliferation of adipose-tissue-derived stem cells (ASC) on fibronectin and analysed the time frame and localization of fibronectin accumulation in the human heart after MI. ASCs were seeded onto fibronectin-coated and uncoated culture wells. The numbers of adhering ASC were quantified after various incubation periods (5-30 min) by using DNA quantification assays. The proliferation of ASC was quantified after culturing ASC for various periods (0-9 days) by using DNA assays. Fibronectin accumulation after MI was quantified by immunohistochemical staining of heart sections from 35 patients, after different infarction periods (0-14 days old). We found that ASC attachment and proliferation on fibronectin-coated culture wells was significantly higher than on uncoated wells. Fibronectin deposition was significantly increased from 12 h to 14 days post-infarction, both in the infarction area and in the border-zone, compared with the uninfarcted heart. Our results suggest that a positive effect of fibronectin on stem cells in the heart can only be achieved when stem cell therapy is applied at least 12 h after MI, when the accumulation of fibronectin occurs in the infarcted heart. © 2008 The Author(s)

    Human platelet lysate as a fetal bovine serum substitute improves human adipose-derived stromal cell culture for future cardiac repair applications

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    Adipose-derived stromal cells (ASC) are promising candidates for cell therapy, for example to treat myocardial infarction. Commonly, fetal bovine serum (FBS) is used in ASC culturing. However, FBS has several disadvantages. Its effects differ between batches and, when applied clinically, transmission of pathogens and antibody development against FBS are possible. In this study, we investigated whether FBS can be substituted by human platelet lysate (PL) in ASC culture, without affecting functional capacities particularly important for cardiac repair application of ASC. We found that PL-cultured ASC had a significant 3-fold increased proliferation rate and a significantly higher attachment to tissue culture plastic as well as to endothelial cells compared with FBS-cultured ASC. PL-cultured ASC remained a significant 25% smaller than FBS-cultured ASC. Both showed a comparable surface marker profile, with the exception of significantly higher levels of CD73, CD90, and CD166 on PL-cultured ASC. PL-cultured ASC showed a significantly higher migration rate compared with FBS-cultured ASC in a transwell assay. Finally, FBS- and PL-cultured ASC had a similar high capacity to differentiate towards cardiomyocytes. In conclusion, this study showed that culturing ASC is more favorable in PL-supplemented medium compared with FBS-supplemented medium

    Changing dominance in mixed profession groups:Putting theory into practice

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    An extended professional identity theory is proposed to enhance interprofessional collaboration. The purpose of this study is to investigate whether comparative feedback on interprofessional interaction can decrease the degree of profession-based dominance and general dominance in mixed profession groups. This observational study comprised a randomized double-blind pretest-posttest control group design with 19 mixed profession groups (10 intervention and nine control groups, each with three dental and three dental hygiene students). All groups received reflective feedback during two consecutive two hour team development meetings. Intervention groups also received comparative feedback. Profession-based dominance concerned the sum of three observation items (conversational turn-taking, dominance and contributing ideas) with a three-point scale: -1 = dental dominance, 0 = no dominance, +1 = dental hygiene dominance. Polychoric correlations confirmed positive associations with the latent trait and an unidimensional underlying structure. Observation items were internally consistent (alpha > .70). General dominance concerned the sum of absolute values of observation items with a minimum value of zero (no dominance) and the maximum value of three (strong dominance). A two-way factorial ANOVA was performed. The results revealed a significant interaction effect with regard to general dominance, F(1,17) = 6.630, p = 0.20 and large effect size (partial eta squared = 0.28). Comparative feedback on interprofessional interaction decreases general dominance in mixed profession groups

    Dutch guideline on total hip prosthesis

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    Contains fulltext : 97840.pdf (publisher's version ) (Open Access

    NADPH oxidases in cardiovascular disease: insights from in vivo models and clinical studies

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    NADPH oxidase family enzymes (or NOXs) are the major sources of reactive oxygen species (ROS) that are implicated in the pathophysiology of many cardiovascular diseases. These enzymes appear to be especially important in the modulation of redox-sensitive signalling pathways that underlie key cellular functions such as growth, differentiation, migration and proliferation. Seven distinct members of the family have been identified of which four (namely NOX1, 2, 4 and 5) may have cardiovascular functions. In this article, we review our current understanding of the roles of NOX enzymes in several common cardiovascular disease states, with a focus on data from genetic studies and clinical data where available
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